Construction of a Potentially Functional circRNA-miRNA-mRNA Network in Intervertebral Disc Degeneration by Bioinformatics Analysis

Abstract

Background. The competing endogenous RNA- (ceRNA-) mediated regulatory mechanisms are known to play a pivotal role in intervertebral disc degeneration (IDD). Our research intended to establish a ceRNA regulatory network related to IDD through bioinformatics analyses. Methods. The expression profiles of circRNA, miRNA, and mRNA were obtained from the public Gene Expression Omnibus (GEO) datasets. Then, we use sequence-based bioinformatics methods to select differentially expressed mRNAs (DEmRNAs), microRNAs (DEmiRNAs), or circRNAs (DEcircRNAs) related to IDD. We used ChEA3 to verify the targets of transcription factors (TFs). Then, we used DAVID to annotate the DEmRNAs. Finally, we constructed a potentially circRNA-miRNA-mRNA network related to IDD by predicting in the database (ENCORI, TargetScan, miRecords, miRmap, and circBank). Results. We identified 31 common DEmRNAs by Venn analysis, of which MMP2 was regarded as the key hub genes. Simultaneously, miR-423-5p and miR-185-5p were predicted as the upstream molecules of MMP2. Furthermore, a total of six DEcircRNAs were predicted as the upstream circRNAs of miR-423-5p and miR-185-5p. Then, a potential circRNA-miRNA-mRNA network related to IDD was constructed by bioinformatics analysis. Conclusion. A comprehensive ceRNA regulatory network was constructed, which was found to be significant in IDD progression.

Targeting Ferroptosis Holds Potential for Intervertebral Disc Degeneration Therapy

“…Harada et al showed that NRF2 could regulate intracellular iron metabolism and was associated with oxidative stress and ferroptosis in macrophages [ 96 ]. Existing evidence has demonstrated that circular RNA, a non-coding RNA, can bind to micro RNA to regulate the expression of its target genes [ 97 , 98 ]. Yu et al suggested that circ_0072464 in bone marrow mesenchymal stem cell (BMSC)-derived extracellular vesicles could increase NRF2 synthesis and alleviate ferroptosis in mouse NP cells by binding to miR-431 [ 14 ].…”

Identification of the circRNA–miRNA–mRNA regulatory network in osteoarthritis using bioinformatics analysis

“…Due to their circular structure, circRNAs identified as biomarkers for diagnosis and prognosis are not affected by RNA exonucleases and become relatively stable (Li et al, 2015;Zhang et al, 2018). Many complex diseases, including non-tumors, are influenced by circRNAs (Xiong et al, 2018;Huo et al, 2021). At present, an increasing number of researchers are focusing on the association between circRNAs and disease occurrence.…”

Targeting Autophagy for Developing New Therapeutic Strategy in Intervertebral Disc Degeneration

“…However, our understanding of the mechanism by which circRNA impacts IVDD is still limited. circRNAs were recently reported to influence pathogenic processes of IVDD including inflammation, ECM metabolism, NP cell proliferation, autophagy, and apoptosis by acting as ceRNAs [ 266 , 299 , 300 , 301 ]. Thus, these newly discovered ceRNA interaction sites could be important targets for IVDD treatment [ 167 , 291 ].…”